Trilayer, extruded medical tubing and medical devices incorporating such tubing

ABSTRACT

The present invention provides a length of trilayer, extruded, medical tubing comprising an outer layer, a core layer, and an intermediate tie layer. The outer layer comprises a polymer that is directly bondable, while the core layer comprises a lubricious polymer. The core layer thus defines a lumen that exhibits the desired characteristics, i.e., low friction for the advancement of a guidewire or catheter through the lumen without comprising the strength and stiffness that is desirable in tubing that is to be used in medical devices. Additionally, the tubing is easily coextruded and yet, is not subject to delamination, thus providing the added advantage of providing a reduction in the overall cost of manufacture.

REFERENCE TO RELATED APPLICATIONS

This application is a completion application of U.S. Provisional patentapplication Ser. No. 60/044,879, filed Apr. 25, 1997, now abandoned.

FIELD OF THE INVENTION

The present invention pertains generally to medical tubing and medicaldevices incorporating such tubing. More specifically, the presentinvention pertains to medical tubing and corresponding medical devicesadapted for percutaneous transluminal use, such as guide catheters,diagnostic catheters such as illustrated in U.S. Pat. No. 5,403,292, andballoon catheters such as illustrated in U.S. Pat. No. 4,762,129.Medical tubing of the present invention is particularly useful tostructurally define the lumen of a catheter, e.g., a rapid-exchangeballoon catheter or an over-the-wire catheter. The tubing of the presentinvention is also useful as an inner member in a stent delivery device.

BACKGROUND OF THE INVENTION

Intravascular catheters are presently in wide clinical use for a varietyof diagnostic and therapeutic purposes. Intravascular catheterizationtherapies, such as angioplasty, atherectomy, and laser irradiation, havebeen developed as alternatives to bypass surgery for treating vasculardiseases or other conditions that occlude or reduce the lumen size ofportions of a patient's vascular system. In particular, balloonangioplasty has proven to be a useful, and in many circumstances, apreferred treatment for obstructive coronary diseases. Also,intravascular diagnostic catheters for angiographics, ultrasonicimaging, and Doppler blood flow measurements for example, have beendeveloped to measure or image the extent of the occlusion of a vessel,(e.g., stenosis). These intravascular diagnostic catheters may be usedin conjunction with the aforementioned therapeutic catheters or may beused in conjunction with more invasive techniques such as coronarysurgery. Intravascular therapeutic and diagnostic catheters haveachieved acceptance because of their effectiveness as well as the factthat their use typically involves a relatively minor surgical procedureas compared to coronary bypass surgery.

However, the effectiveness of the techniques employing these cathetersmay at times be dependent upon the positioning of the catheter into thevascular system of a patient via an incision at an accessible locationwhich may be remote from the site of occlusion or stenosis. Typically,for example, the intravascular catheter may be introduced into thefemoral artery through an incision at the groin and then advancedthrough the femoral artery to the desired distal coronary site. Becauseof the small size of some of these vessels and the tortuous passagesthrough the vessels, positioning of a catheter through a patient'svasculature can be a difficult and time consuming task. Furthermore, thecatheters must be able to traverse these tortuous pathways in a manneras atraumatic to the patient as possible. Therefore, in order to limitinsertion time and discomfort to the patient, intravascular catheterswill preferably have several performance characteristics.

First of all, an intravascular catheter should exhibit good torquecontrol such that manipulation of a proximal portion of the catheter isresponsively translated to the tip or distal portion of the catheter.Moreover, the catheter should have sufficient strength in thelongitudinal direction so as not to kink or fold as it is advancedthrough the vascular system. Also, for some types of intravascularcatheters, it is desirable to maximize the inner diameter relative tothe outer diameter, i.e., to make the lumen as large as practicallypossible. Specifically, for example, diagnostic catheters generallypossess a relatively large lumen to allow fluids, such as radiopaquecontrast fluid, to be injected therethrough and out the distal end sothat the area of the vascular system under investigation can be viewedfluoroscopically.

Additionally, if the catheter is a dilation catheter, the outer surfaceof the tubing to be used in an intravascular catheter must be bondableto balloon material. Although the tubing may be bonded to the balloonwith adhesive, this is not optimal as the adhesive may fail.Additionally, the adhesive undesirably adds to the surface profile ofthe catheter. Thus, it is preferable that the outer surface of thetubing of the catheter be directly bondable to the balloon material,such as by fusion bonding, described in U.S. Pat. Nos. 5,501,759 and5,267,959.

Finally, catheter balloons are now being inflated to higher pressuresthan has been previously conventional in the art. For example, untilrecently, balloon inflation pressures typically averaged approximately12 atmospheres. However, one current trend involves inflating balloonsto pressures as high as 28 atmospheres. This relatively high pressuretends to stretch and constrict tubing if the tubing is too weak. Insevere cases, the tubing could rupture. Thus, in order to be useful in aballoon catheter involving higher pressures, the tubing must be strongenough to withstand this higher pressure without collapsing orrupturing.

The internal lumen surface of intravascular catheters is subject toperformance demands as well. For example, an important function of theinternal lumen surface of intravascular catheters is to provide very lowsurface friction between the catheter and a guidewire and/or treatmentdevice slidably engaging the lumen surface. The low friction internalsurface facilitates advancement of the catheter over the guidewire orthe advancement of the treatment device through the catheter lumen, asthe case may be. Lubricity is especially critical in the curved portionof guide catheters. The low friction internal surface has typically beenprovided by the use of a lubricious polymer, e.g.,polytetrafluoroethylene or the like, as the internal surface material,or alternatively, by coating the internal lumen surface of the catheterwith a friction reducing material, such as liquid silicone.

In sum, catheter tubing should possess a combination of the desiredcharacteristics of strength, pushability, torqueability, bondability andlubricity. However, such a combination of characteristics has not beenachieved satisfactorily with tubing comprising only a single material.First of all, medical tubing formed from an inherently lubriciouspolymer tends to be difficult to effectively bond to the material ofconventional balloons due to the chemical incompatibility between thematerials to be bonded. On the other hand, polymer materials thatdemonstrate good bonding characteristics with balloons typically must becoated with a lubricant on the interior surface so that the interiorsurface is sufficiently lubricious, necessitating an additionalmanufacturing step. Furthermore, such lubricants tend to wear off, sothat lubricity is diminished over time.

The prior art also describes several attempts to provide the desiredcharacteristics by utilizing multilayered tubing in intravascularcatheters. Conventionally, such multilayered tubing comprises an outerlayer of a bondable material such as nylon, polyethylene, polyurethane,or poly(ethylene terephthalate) and an inner layer of a lubriciousmaterial such as polytetrafluoroethylene (PTFE) or other lubriciouspolymer, e.g., high density polyethylene. For example, U.S. Pat. No.5,538,510 describes a coextrudable, flexible tubing which comprises anouter layer and an inner layer, the two layers being different materialsand being covalently bonded to each other. Specifically, the patentpurports to provide a length of tubing with the desired combination ofproperties by using a lubricious polymer as the inner layer, and a stiffpolymer as the outer layer. The patent discloses that the flexibletubing is coextrudable and, furthermore, that the lumen of the tubing issufficiently lubricious so as to obviate the use of a separate lowfriction sleeve and/or coating. Additionally, U.S. Pat. No. 4,707,389describes a multi-layered tube composed of an outer layer ofethylenevinylacetate (EVA) and an inner layer of polyvinychloride (PVC),bonded together by a bonding layer. Finally, U.S. Pat. No. 3,561,493discloses a multi-layered tubing in which the inner and outer layers arewelded together by a precompounded layer of the two different polymers.

Although each of these patents purport to provide tubing and/or medicaldevices with the desired characteristics, problems still remain withexisting multilayer tubing structures. For example, the low frictionpolymeric materials capable of providing a sufficiently lubricious lumenare generally chemically incompatible with the polymeric materials thatare capable of providing adequate performance as the catheter outerlayer. As a result of this chemical incompatibility, these differentclasses of materials do not form significant bonds with each other, evenupon coextrusion, and thus, tubing comprising layers of these dissimilarmaterials tends to be subject to delamination. Further, substantialdifferences between the mechanical properties of the two classes ofpolymer materials further exacerbates this incompatibility problem.

There is thus a need in the art for medical tubing and medical devicesincorporating such tubing that exhibit the desired characteristics ofstrength, pushability, torqueability, bondability and lumen lubricity.These and other objects are accomplished by the present invention, ashereinafter described.

SUMMARY OF THE INVENTION

According to the present invention, the above objectives and otherobjectives apparent to those skilled in the art upon reading thisdisclosure are attained by the present invention which is drawn totrilayered tubing as well as to a medical device suitable forpercutaneous transluminal use comprising the tubing. More specifically,it is an object of the present invention to provide coextruded,flexible, trilayered tubing, wherein the three layers are firmly bondedtogether such that the layers resist delamination under operatingconditions both normal and extreme (e.g., high balloon pressures of upto 28 atmospheres or more) and furthermore, wherein the materials thatcomprise the three layers provide the tubing with the desirablecharacteristics for tubing that is to be used in a medical devicesuitable for percutaneous transluminal use.

Generally, the present invention provides a length of coextruded,flexible tubing that meets the needs and objectives describedhereinabove, by virtue of a multilayer structure. Specifically, themultilayer structure comprises a core layer of a lubricious polymericmaterial, an outer layer comprising directly bondable (defined below)polymer, and an intermediate tie layer comprising a polymer havingpendant functionality capable of adhering the lubricious material of thecore layer to the directly bondable material of the outer layer. In thismanner, the intermediate tie layer provides a strong connection betweenthe core layer and the outer layer.

In preferred embodiments, the glass transition temperature (T_(g))characteristics of the intermediate tie layer are selected to beinbetween those of the core layer and the outer layer. Specifically, itis preferred that the glass transition temperatures vary only graduallyfrom the core layer to the outer layer in order to provide a stage-wisetransition of mechanical characteristics from the material of the outerlayer to the material of the core layer. Preferably, the glasstransition temperature of each layer will be from 85% to 115% of theglass transition temperature of the material(s) adjacent to it. Byproviding a gradient in the T_(g) from the core layer to the outerlayer, a more stable, more compatible, trilayered tubing is providedthat possesses the desired characteristics of strength, pushability,torqueability, bondability, and a lubricious lumen, while alsodemonstrating dramatically improved resistance against delamination.

The present invention thus provides a length of coextruded, flexibletubing comprising an outer layer having a first glass transitiontemperature, an intermediate tie layer having a second glass transitiontemperature, and a core layer having a third glass transitiontemperature. Preferably, the first glass transition temperature isgreater than the second glass transition temperature, which ispreferably greater than the third glass transition temperature.Additionally, it is preferred that the outer layer be comprised of amaterial that is directly bondable to conventional balloon materials. Itis further preferred that the core layer is comprised of a material thatis lubricious and that the intermediate tie layer is comprised of amaterial that comprises functionality capable of adhering to both thematerial of the outer layer and the material of the core layer.

In another aspect, there is also provided a medical device suitable forpercutaneous transluminal use comprising the tubing of the presentinvention and a radially expansive component operationally coupled tothe tubing. For example, the tubing of the present invention may beutilized to define the guidewire lumen of a balloon catheter. Morespecifically, the trilayer tubing of the present invention may definethe guidewire lumen of an over-the-wire catheter, i.e., where theguidewire lumen as defined by the trilayered tubing runs the entirelength of the catheter. The tubing of the present invention may alsodefine the guidewire lumen of a rapid exchange catheter, i.e., whereinone end of the guidewire lumen as defined by the tubing of the presentinvention extends through the distal end of the catheter and theopposite end exits through an outer wall of the catheter. Additionally,the trilayered tubing of the present invention may be utilized to formthe inner member of a stent- delivery device, wherein a stent isreleasably mounted to the tubing of the present invention.

As used herein, the phrase "direct bond" (or "directly bondable") ismeant to indicate a bond between two materials that requires no bondingsubstance, i.e, adhesive, interposed between the materials (or materialsthat are so bondable). Additionally, the term "lubricious" as applied tothe materials herein is meant to indicate a material that has a kineticcoefficient of friction (steel on polymer) of less than about 0.5. Asused herein, "elastomeric" is meant to indicate that property of amaterial that allows the material to be stretched to at least twicetheir original length and to recover its original shape partially orcompletely after the deforming force has been removed. "Glass transitiontemperature" or "T_(g) " as used herein and as is generally known tothose of skill in the art, refers to that temperature at which anamorphous material changes from a brittle vitreous state to a plasticstate and may be determined by Differential Scanning Calorimetry (DSC).Finally, as used herein, the phrase "acid-functional" is meant toindicate materials that have pendant acidic functional groups.

BRIEF DESCRIPTION OF THE DRAWINGS

The above mentioned and other advantages of the present invention, andthe manner of attaining them, will become apparent and the inventionitself will be better understood by reference to the followingdescription of the embodiments of the invention taken in conjunctionwith the accompanying drawings, wherein:

FIG. 1 is an enlarged, cross-sectional view of one embodiment of tubingin accordance with the present invention;

FIG. 2 is a longitudinal sectional view of an over-the-wire angioplastycatheter in accordance with the present invention;

FIG. 3A is an enlarged, cross-sectional view taken along line A--A ofFIG. 2;

FIG. 3B is an enlarged, cross-sectional view taken along line B--B ofFIG. 2;

FIG. 3C is an enlarged, cross-sectional view taken along line C--C ofFIG. 2;

FIG. 4 is a longitudinal sectional view of a rapid exchange angioplastycatheter in accordance with the present invention;

FIG. 5A is an enlarged, cross-sectional view taken along line A--A ofFIG. 4;

FIG. 5B is an enlarged, cross-sectional view taken along line B--B ofFIG. 4;

FIG. 5C is an enlarged, cross-sectional view taken along line C--C ofFIG. 4;

FIG. 6 is a schematic view of an extrusion system capable of extrudingthe tubing of the present invention; and

FIG. 7 is a longitudinal sectional view of a stent delivery device inaccordance with the present invention

DETAILED DESCRIPTION OF THE INVENTION

The embodiments of the present invention described below are notintended to be exhaustive or to limit the invention to the precise formsdisclosed in the following detailed description. Rather the embodimentsare chosen and described so that others skilled in the art mayappreciate and understand the principles and practices of the presentinvention.

According to the present invention, trilayer tubing 10 is illustrated incross-sectional view in FIG. 1. In accordance with the presentinvention, tubing 10 comprises outer layer 16, intermediate tie layer14, and core layer 12, the polymeric materials of the outer, tie andcore layers typically being different and being formed preferably bycoextruding. Inner surface 13 of trilayer tubing 10 defines lumen 15.

Outer layer 16 is preferably comprised of at least one directly bondablepolymer. That is, outer layer 16 is preferably comprises of at least onepolymer selected so as to be directly bondable to the balloon by atechnique such as fusion bonding. A wide variety of polymers may beincorporated into outer layer 16. Preferably, the material chosen foruse in outer layer 16 will be thermoplastic, so as to be more easilyextrudable. It is further preferred that the material chosen for use inouter layer 16 will be elastomeric. Generally, preferred polymers foruse in outer layer 16 have a weight average molecular weight in therange of from about 40,000 to about 100,000.

Outer layer 16 may preferably comprise a polyester, a polyamide orcombinations thereof Exemplary polyesters which are suitable for use inouter layer 16 include polyesters containing both polyether andpolyester segments. Particularly suitable are the family of polyetherpolyesters commercially available under the trade name Hytrel® from E.I. DuPont De Nemours and Company, Wilmington, Del. Also well-suited foruse in outer layer 16 of tubing 10 of the present invention are thefamily of polyesters available under the trade name Arnitel® from DSMEngineering Plastics, Evansville, Ind.

Polyamides suitable for use in outer layer 16 in tubing 10 of thepresent invention include Nylon 12, Nylon 6/6 or other nylon copolymers,as well as polyether block amides. An example of a commerciallyavailable polyamide suitable for use in outer layer 16 in the tubing 10of the present invention is available under the trade name PEBAX® fromAtochem Inc., Glen Rock, N.J.

Core layer 12 is preferably made of at least one lubricious polymericmaterial to facilitate the advancement over a guidewire or advancementof a separate, smaller catheter through lumen 15 of tubing 10. Althoughit is preferred that core layer 12 be sufficiently lubricious withoutsuch a coating, a solid or liquid lubricant may coat the surface oflumen 15 as structurally defined by core layer 12, and thus such acoating is understood to be within the scope of the present invention.As discussed hereinabove, lubricious materials, as used herein,preferably are those materials with a kinetic coefficient of friction(steel on polymer) of less than about 0.5. Generally, preferredlubricious polymers have a weight average molecular weight in the rangeof from about 80,000 to about 300,000.

As representative examples, the at least one lubricious polymericmaterial incorporated into core layer 12 may preferably be selected froman olefinic polymer, a fluorinated polymer, or combinations thereof.More preferably, the material of core layer 12, if an olefinic polymer,may comprise a high density polyethylene, an ultra high densitypolyethylene, a low density polyethylene, a linear low densitypolyethylene, or combinations thereof. Such polyethylene resins arecommercially available from the Quantum Chemical Company, Cincinnati,Ohio, under the trade name Petrothene® LS 5060-00 and LM 6007-00.Additional materials that are believed to be suitable in core layer 12include fluorinated polymers such as polytetrafluorethylene (PTFE) andpolyvinylidenefluoride (PVDF). Because PVDF is much easier and practicalto extrude than PTPE, PVDF is presently a more preferred fluoropolymer.

Intermediate tie layer 14 is interposed between outer layer 16 and corelayer 12, preferably in a manner such that neither the inner or outersurface of intermediate tie layer 14 is exposed. Intermediate tie layer14 is preferably made of a polymeric material comprising functionalitycapable of adhering outer layer 16 to core layer 12. In this manner,intermediate tie layer 14 aggressively links the two other layerstogether with a strong connection that resists delamination. Generally,preferred polymers for use in intermediate tie layer 14 have a weightaverage molecular weight in the range of from about 40,000 to about250,000.

Additionally, due to the extreme difference in mechanical propertiesdiscussed above, intermediate tie layer 14 is preferably made of amaterial selected to have thermal characteristics, e.g., a glasstransition temperature, inbetween those of core layer 12 and outer layer16 so as to provide a step-wise transition in mechanical properties fromthe material of outer layer 16 to those of the material of core layer12. Intermediate tie layer 14 thus operates to reduce the stresses thatmight otherwise be created as a result of the differing materials ofouter layer 16 and core layer 12 if the intermediate tie layer 14 of thepresent invention were not used. By virtue of this relationship and thefunctionality of the material of the intermediate tie layer 14, layers12, 14 and 16 are strongly adhered together in a manner resistant todelamination.

Thus, any polymer having a having functionality capable of adhering toboth core layer 12 and outer layer 16 may be advantageously used asintermediate tie layer 14. Representative examples of such polymersinclude olefinic and other free radically polymerized polymers havingone or more functional groups selected from carbon-carbon double bonds,vinyl esters, amine groups, acid groups such as --COOH, --SO₃ H, --PO₃H, the salts of such acids, and the like, an anhydric moiety such as##STR1## or combinations thereof, and the like.

For example, functionalized olefinic materials suitable for use in theintermediate tie layer 14 of tubing 10 include olefins such aspolyethylene of varying densities, polypropylene, or polyethylene vinylacetate that have been formed from olefinic monomers copolymerized witha copolymerizable monomer, e.g., maleic acid, having the desiredfunctionality. Other unsaturated carboxylic acids such as fumaric acid,cinnamic acid, crotonic acid, linoleic acid, or the like may also beused as a substitute for maleic acid. These acid functional olefinicpolymeric materials are described, for example, in U.S. Pat. No.5,538,510, incorporated herein by reference.

Other examples of acid and anhydride functional polymers that arebelieved to be suitable for use in intermediate tie layer 14 includeacid functional ethyl vinyl acetate resins, acid functional ethyleneacrylate polymers, anhydride functional ethylene acrylate copolymers,anhydride functional ethyl vinyl acetate copolymers, acid and acrylatefunctional ethyl vinyl acetate resins, anhydride functional ethyl vinylacetate copolymers, and anhydride functional ethyl vinyl acetate resins.In particular, suitable acid and anhydride functional polymers arecommercially available under the trade name of Bynel® from E. I. DuPontDe Nemours, Wilmington Del.

Functionalized polyethylenes are also suitable for use in intermediatetie layer 14. Examples of other such functionalized polyethylenes whichare suitable for use in intermediate tie layer 14 include, but are notlimited to, functionalized high density polyethylene and functionalizedlinear low density polyethylene. Such functionalized polyethylenes arecommercially available from the Quantum Chemical Corporation under thetrade name of Plexar®.

Additionally, the material of intermediate tie layer 14 may be a freeradically polymerized copolymer of monomers comprising ethylene and analkyl (meth)acrylate. Ethylene-methyl (meth)acrylate copolymers havingester functionality that are believed to be suitable as intermediate tielayer 14 are commercially available under the trade name EMAC® (e.g.,EMAC® SP 2205 and 2260) from Chevron Company, Houston, Tex.

As mentioned hereinabove, the polymeric materials of the outer, core andintermediate tie layers 16, 12, and 14, respectively, are preferablycomprised of materials with glass transition temperatures that aresubstantially similar so as to facilitate coextrusion and to help reducethe tendency of undue stress to build between the layers in theresultant tubing. Preferably, the glass transition temperature (T_(g))of each layer will be from 85% to 115% of the glass transitiontemperature of the material(s) adjacent to it. In preferred embodiments,the T_(g) of the functionalized polymer of intermediate layer 14 isabout 1 to 1.15 times greater than the polymer of outer layer 16, andthe T_(g) of the lubricious polymer in core layer 12 is about 1 to 1.15times greater than the functionalized polymer of intermediate tie layer14.

Representative combinations of materials suitable for use in tubing 10of the present invention are shown in Table 1, hereinbelow.

                  TABLE 1                                                         ______________________________________                                        Core Layer (12)                                                                          Intermediate Tie Layer (14)                                                                    Outer Layer (16)                                  ______________________________________                                        polyethylene                                                                             functionalized polyethylene                                                                    polyester                                         polyethylene                                                                             functionalized polyethylene                                                                    polyamide                                         polyethylene                                                                             ethylene-methyl acrylate                                                                       polyester                                                    copolymers                                                         polyethylene                                                                             ethylene-methyl acrylate                                                                       polyamide                                                    copolymers                                                         polyethylene                                                                             acid/anhydride functionalized                                                                  polyester                                                    vinylic copolymer                                                  fluorinated polymer                                                                      functionalized polyethylene                                                                    polyester                                         fluorinated polymer                                                                      functionalized polyethylene                                                                    polyamide                                         fluorinated polymer                                                                      ethylene-methyl acrylate                                                                       polyester                                                    copolymers                                                         fluorinated polymer                                                                      ethylene-methyl acrylate                                                                       polyamide                                                    copolymers                                                         fluorinated polymer                                                                      acid/anhydride functionalized                                                                  polyester                                                    vinylic copolymer                                                  ______________________________________                                    

The thicknesses of layers 12, 14 and 16 will vary depending upon desiredapplications. For example, when used to define the guidewire lumen of anangioplasty catheter, the core layer 12 of tubing 10 will preferablyhave a thickness of from about 0.01 mm to about 0.05 mm, while theintermediate tie layer 14 is preferably of a thickness of from about0.006 mm to about 0.03 mm and outer layer 16 is preferably from about0.01 mm to about 0.05 mm thick. More preferably, core layer 12 will befrom about 0.01 mm to about 0.04 mm thick, intermediate tie layer 14will be from about 0.003 mm to about 0.03 mm and outer layer 16 will befrom about 0.01 mm to about 0.04 mm.

Additionally, the diameter of tubing 10 will vary depending upon theend-use application. Typically, the overall, or outside, diameter(D_(o)) is typically between 0.5 mm and 0.7 mm, and will preferably befrom about 0.55 mm to about 0.63 mm. Core layer 12 will preferablydefine a lumen, such as a lumen adapted to receive a guidewire. Theinside diameter (D_(i)) of the lumen so formed is typically from about0.4 mm to about 0.6 mm, and will preferably be from about 0.43 mm toabout 0.51 mm.

The tubing of the present invention may be used, for example, in medicaldevices suitable for percutaneous transluminal use, such as guidecatheters, diagnostic catheters, or those medical devices in which aradially expansive component is to be therapeutically deployed, e.g.,stent delivery devices or balloon catheters. In one embodiment of theinvention, for example, the tubing of the present invention may beutilized to define a guidewire lumen in an over-the-wire ballooncatheter 220, as illustrated in FIGS. 2 (where the balloon isillustrated in its deployed state), 3A, 3B and 3C. As illustrated,catheter 220 comprises an outer catheter tubing 222 which connects withballoon 224 at tubing distal end 226. Outer catheter tubing 222terminates at its distal end 226, where outer catheter tubing 222connects with the proximal end 292 of balloon 224. Outer catheter tubing222 defines lumen 294.

The aforementioned connection, and any other connection, weld or bondmentioned herein, may be established by any method that forms fluidtight seals between the materials at the desired bond site, e.g., aswith adhesive, or by direct bonding. However, it is generally preferredthat these connections be established by direct bonding. Direct bondingis considered advantageous since the use of an intermediate adhesivelayer is thereby avoided. The use of adhesive is a less desirablealternative as adhesive layers add to the thickness and rigidity of themedical device at the bond site. Additionally, many adhesives presentbiocompatiblity issues.

Thus, it is preferred that outer catheter tubing 222 is directly bondedto balloon 224 at distal end 226. These direct bonds may be establishedby any method known to those of ordinary skill in the art thateffectively forms fluid tight seals between the materials to be bonded.For example, the direct bonds may be established by conductive,convective, or radiative heating, combinations thereof, of any one ofthese heating methods used in combination with pressure applied to thebond area. Furthermore, the direct bonds may be formed by fusionbonding. Fusion bonding using laser energy is disclosed in U.S. Pat.No.s 5,267,959 and 5,501,759; the disclosures of which are incorporatedby reference herein.

Also, catheter 220 comprises an inner catheter tubing 210 which defineslumen 234. Inner catheter tubing 210 extends through lumen 294 of outercatheter tubing 222, thus defining a generally annular space 230 betweenouter catheter tubing 222 and inner catheter tubing 210. Generally,annular space 230 extends along the catheter 220 between outer cathetertubing 222 and inner catheter tubing 210, to terminate in communicationwith the interior 296 of balloon 224. Inner catheter tubing 210,however, extends through balloon 224 as shown in FIG. 1, being bonded toballoon 224 at distal end 232 in such a manner that the lumen 234 ofinner catheter tubing 210 is open at distal end 232. Advantageously andpreferably, distal end 298 of inner catheter tubing 210 is directlybonded to balloon 224 at distal end 232.

Although inner catheter tubing 210 is in the form of trilayer tubing ofthe present invention as described hereinabove with respect to FIG. 1,the three layers have not been individually illustrated in FIG. 2 forpurposes of clarity. As previously stated, the material of the corelayer 12 (illustrated in FIG. 1) preferably comprises a lubriciousmaterial that defines a lubricious inner lumen. By providing alubricious inner lumen, the advancement of catheter 220 over a guidewireor the advancement of a separate, smaller catheter, for example, throughlumen 234 of tubing 210 is facilitated.

Because of the lubricious nature of the polymer of the core layer 12,the polymer that is to comprise outer layer 16 may be selected tooptimize other characteristics of catheter 220 rather than to providethe necessary lubricity to the inner lumen of catheter 220. For example,the polymer of outer layer 16 may be chosen on the basis of bondabilityto the desired balloon material. In preferred embodiments, at least aportion of the monomeric segments of the polymer of outer layer 16correspond to at least a portion of the monomeric segments of thedesired balloon material. For example, if outer layer 16 comprises apolyether polyester, i.e. a polymer comprising polyester and polyethersegments, it would be preferred that the balloon comprise a materialwith polyether or polyester segments, such as polyethylene pterphthalate(PET).

In a second embodiment of the present invention, the trilayer, medicaltubing of the present invention may be used as the inner catheter tubing410 in a rapid exchange balloon catheter 420, as illustrated in FIGS. 4,5A, 5B, and 5C. Again, although inner catheter tubing 410 is in the formof trilayer tubing of the present invention as described hereinabovewith respect to FIG. 1, the three layers have not been individuallyillustrated in FIG. 4 for purposes of clarity.

Catheter 420 comprises a tubular proximal shaft 460, a tubular stem 462,inner catheter tubing 410 and a balloon 424. Stem 462 is in fluidcommunication with proximal shaft 460 and is bonded to the distal end492 of proximal shaft 460. Inner catheter tubing 410 defines guidewirelumen 434. Inner catheter tubing 410 extends from distal portion 492 ofproximal shaft 460 and through lumen 464 of stem 462, beyond the distalend 494 of stem 462, and through balloon 424. Inner catheter tubing 410additionally comprises a proximal end 496 open to the outside of thecatheter 420 at skive 466. Inner catheter tubing 410 and stem 462 arepreferably directly bonded together at weld 4102 proximal to balloon424. At the skive 466, the distal end 492 of proximal shaft 460, theproximal end 496 of tubular stem 462, and the proximal end 4100 of innercatheter tubing 410 are directly bonded together. Inner catheter tubing410 is off-center at skive 466 but becomes approximately centeredthroughout the remaining length of stem 462. Balloon 424 is arrangedcoaxially around inner catheter tubing 410 with the proximal neck 4104of balloon 424 directly bonded to the distal end of stem 462 at theouter surface thereof. The distal neck 432 of balloon 424 is directlybonded to the distal end 4106 of inner catheter tubing 410, togetherforming the catheter tip 468.

In a third embodiment of the present invention, the tubing of thepresent invention may be used as the inner member 710 in a stentdelivery device, as illustrated in FIG. 7, in which the stent isillustrated in its deployed state. As was the case with FIGS. 2 and 4,although inner catheter tubing 710 is in the form of trilayer tubing ofthe present invention as described hereinabove with respect to FIG. 1,the three layers have not been individually illustrated in FIG. 7 forpurposes of clarity.

Stent delivery device 720 comprises a tubular outer sleeve 722 and ahollow, flexible core element 710. Outer sleeve 722 has integral handle734 attached at its proximal end. The distal end 724 of outer sleeve 722is positioned within a body canal 738. Disposed axially within outersleeve 722 is hollow, flexible core element 710 having a handle 736 atits proximal end. The distal end 728 of the core element 710 has astepped up diameter where it meets the distal end 724 of outer sleeve722 so that it provides a smooth transition at the distal end 724 ofouter sleeve 722, and is also located within body canal 738. A guidewire 730 passes axially through the hollow core. Attached around theperiphery of the core element 710 at its distal end 728 is grip member732 which releasably grips a self-expanding stent 726 (shown partlydeployed).

The tubing 10 of the present invention can be manufactured bycoextrusion as schematically illustrated in FIG. 6. Although threeextruders typically are used, one for each layer 12, 14 and 16, only oneextruder 605 is shown for purposes of clarity. In the case of suchtrilayer extrusion, the three desired materials can converge through onedie 646 to create a single trilayer tube. Referring to the operation ofextruder 605, which is representative of all three extruders, pellets(not shown) of suitable material can be gravitationally fed from ahopper 640 into the feed section 654 of extruder 605. There, the pelletscome into contact with rotating screw 656. The pellets are then conveyedthrough barrel 658 by rotating screw 656. The pellets are heated byelectrically heated barrel 658 and by the frictional and shear action ofthe screw 656 as it turns in the barrel 658. Eventually, as the pelletsmove down the length of the barrel 658, the pellets are transformed intoa molten phase which is then forced out of a coextrusion die 646 alongwith molten material from the other two extruders to create a coextrudedtube 660. The tube 660 is then drawn down into cooling trough 648 tocool and set the tube 660 into a predetermined thickness and diameter bymeans of puller 650. Once the tube 660 is cooled and pulled it is readyfor collection, i.e., with a cutter (not shown) or coiler 652, and use.

    ______________________________________                                        For example, the extrusion line may comprise the following equipment:         2        3/4" Davis Standard Extruder (for inner and outer layers)            1        1/2-3/4" Davis Standard Extruder (for middle layer)                  1        3-layer Genca Crosshead (tri-die, commercially available                      from Genca Extrusion Technology, Clearwater, Florida)                1        Water Bath                                                           1        Puller RDN                                                           1        Laser gauge Zumbach (to check dimensions).                           Process conditions include:                                                   Temperatures                                                                           370°-470° F.                                           Pressures                                                                              1000-3000 psi                                                        Line Speed                                                                             50-200 fpm                                                           ______________________________________                                    

The following examples, while not intended to be limiting, illustratevarious features of the present invention.

Example 1

The following experiment was performed to investigate the effects ofirradiation sterilization on an EDPE layer of trilayer tubing.

Specifically, one hundred pieces of 6" tubing made of Hytrel® 63D as theoutside layer, Plexar® 209 as the middle layer, and HDPE 6007 as theinside layer were irradiated (0.0185" overall ID×0.0265" overall OD).Twenty pieces were irradiated at dosages of 20 Mrad, 30 Mrad, 40 Mrad,50 Mrad, and 60 Mrad, respectively. Control samples receiving noirradiation were also provided.

Differential Scanning Calorimetry (DSC) was used to determine thethermal properties of the three different layers. No significantdifferences were seen between control samples or samples at any of thedosage levels.

Solids rheology testing was also performed with similar conclusions. Nosignificant changes were detected between the samples at any of thedosage levels.

To test the effect of the irradiation on the bondability of the outersurface of the tubing to balloon material, PET balloons were bonded tothe tubing by fusion bonding and then the bond site skived and inspectedfor delamination. No significant differences in the amount ofdelamination were noted between any of the dosage levels and thecontrol.

It was concluded that irradiating with electron-beam irradiation thetrilayer tubing does not adversely affect resistance to delamination nordoes irradiation increase the melt resistance of the HDPE layer.

Example 2

Tests were performed to determine if trilayer tubing can be effectivelylaser-bonded to angioplasty balloons comprising polyethyleneterphthalate(PET) as an inner balloon layer. Trilayer tubing having an innerdiameter (ID) of 0.0182 inches and an outer diameter (OD) of 0.0236inches and including Hytrel® 7246 as the outside layer, Plexar® 209 asthe middle layer, and HDPE 5006 as the inside layer, was tested.

The outer layer of the tubing was fusion bonded to PET of balloon usinglaser energy as described in Forman, U.S. Pat. No. 5,501,759. Weld spotsize was held constant at 2.215 inches and RPM was held constant at2500. Power was varied between 2.0, 3.0, and 4.0 Watts, respectively.

It was concluded that effective bonds were achieved at all power levels.No bonds failed before balloon burst occurred. Also, times for proximaland distal bonds were set for each power level, despite the variation inwall thickness between parts. The best bonds were achieved with the 3.0Watt power setting, based on visual examination after burst.

Example 3

Crush tests were performed on tubing of the present invention made ofHytrel® 7246 as the outside layer, Plexar® 209 as the middle layer, andHDPE 6007 as the inside layer.

Start Pressure: 147.0 (10 ATM) Stop Pressure: 411.6 (28 ATM)

Increment: 14.7 PSI Hold Time: 15 seconds

    __________________________________________________________________________              RESISTANCE                                                                           LOCKS                                                                              DAMAGE                                                                              AFTER INFLATION TO 28 ATM                         ID"  OD"  FELT AT:                                                                             UP AT:                                                                             OBSERVED                                                                            AVG OD"                                                                            MIN. OD"                                                                           MAX OD"                                 __________________________________________________________________________    0.0169                                                                             0.0225                                                                             352.8  Does Not                                                                           No Damage                                                                           0.0226                                                                             0.0224                                                                             0.0227                                            (24 ATM)                                                                             Lock                                                         0.0169                                                                             0 0224                                                                             367.5  Does Not                                                                           No Damage                                                                           0.0227                                                                             0.0226                                                                             0.0228                                            (24 ATM)                                                                             Lock                                                         0.0172                                                                             0.0232                                                                             352.8  Does Not                                                                           No Damage                                                                           0.0231                                                                             0.0228                                                                             0.0234                                            (24 ATM)                                                                             Lock                                                         0.0169                                                                             0.0226                                                                             382.2  Does Not                                                                           No Damage                                                                           0.0228                                                                             0.0226                                                                             0.0229                                            (26 ATM)                                                                             Lock                                                         0.017                                                                              0.0227                                                                             367.5  Does Not                                                                           No Damage                                                                           0.0228                                                                             0.0225                                                                             0.023                                             (25 ATM)                                                                             Lock                                                         x = .0170                                                                          x = .023                                                                           x = 364.56        x = .0228                                                                          x = .0226                                                                          x = .0230                               s = .0001                                                                          s = .0003                                                                          s = 12.30         s = .0002                                                                          s = .0001                                                                          s = .0003                               __________________________________________________________________________     x = mean.                                                                     s = standard deviation.                                                  

"Resistance felt" means the point when the tube collapsed enough so thatan increase in friction was felt on a guidewire by an operator pullingit through the tubing. "Locks up" is meant to indicate the point atwhich the guidewire is completely stuck due to the collapse of the tube.

Example 4

Crush tests were performed on tubing of the present invention made ofHytrel® 7246 as the outside layer, Plexar® 209 as the middle layer, andHDPE 6007 as the inside layer.

Start Pressure: 147.0 (10 ATM) Stop Pressure: 499.8 (34 ATM)

Increment: 14.7 PSI Hold Time: 15 seconds

    __________________________________________________________________________              RESISTANCE                                                                           LOCKS UP                                                                            DAMAGE                                                                              AFTER INFLATION TO 28 ATM                        ID"  OD"  FELT AT:                                                                             AT:   OBSERVED                                                                            AVG OD"                                                                            MIN. OD"                                                                           MAX OD"                                __________________________________________________________________________    0.0169                                                                             0.0228                                                                             367.5  470.4 Slightly Oval                                                                       0.0228                                                                             0.0224                                                                             0.0232                                           (25 ATM)                                                                             (32 ATM)                                                     0.0168                                                                             0 0232                                                                             382.2  470.4 Slightly Oval                                                                       0.0228                                                                             0.0226                                                                             0.023                                            (26 ATM)                                                                             (32 ATM)                                                     0.0171                                                                             0.0235                                                                             382.2  470.4 Slightly Oval                                                                       0.0232                                                                             0.0225                                                                             0.0235                                           (26 ATM)                                                                             (32 ATM)                                                     0.0168                                                                             0.0227                                                                             367.5  455.7 Slightly Oval                                                                       0.0226                                                                             0.0222                                                                             0.023                                            (25 ATM)                                                                             (31 ATM)                                                     0.0171                                                                             0.023                                                                              367.5  470.4 Slightly Oval                                                                       0.0228                                                                             0.0223                                                                             0.0231                                           (25 ATM)                                                                             (32 ATM)                                                     x = .0169                                                                          x = .023                                                                           x = 373.38                                                                           x = 467.46  x = .0228                                                                          x = .0224                                                                          x = .0232                              s = .0002                                                                          s = .0003                                                                          s = 8.05                                                                             s = 6.57    s = .0002                                                                          s = .0002                                                                          s = .0002                              __________________________________________________________________________     x = mean.                                                                     s = standard deviation.                                                  

"Resistance felt" and "lock-up" have the same meanings as in Example 3.

Example 5

Tests were performed to determine the tensile strength effect ofannealing at different temperatures and times for 0.0185" ID×0.0235" ODtrilayer tubing. Material composition of the tubing is Hytrel® 7246 asthe outside layer, Plexar® 209 as the middle layer, and HDPE 6007 as theinside layer. Five unannealed tubes of the same size were tested andfound to have an average peak load of 1.255 lbs (standard deviation0.047).

    __________________________________________________________________________                    % Strain                                                      Annealing                                                                            Peak                                                                              Peak @ Break                                                                            Yield                                                                              % Strain                                            time, temp                                                                           Load lb.                                                                          Stress psi                                                                         %    Stress psi                                                                         @ yield %                                                                          Modulus psi                                    __________________________________________________________________________    1 hr., 100° C.                                                                1.4 8451.5                                                                             367.8                                                                              4578.1                                                                             11.724                                                                             93329                                          4 hr., 100° C.                                                                1.4 8520.7                                                                             368.9                                                                              4665.5                                                                             11.273                                                                             99734.7                                        2.5 hr., 110° C.                                                              1.4 8728.6                                                                             385.7                                                                              4710.7                                                                             11.694                                                                             96051.8                                        1 hr., 120° C.                                                                1.5 9041.8                                                                             389.2                                                                              4885.3                                                                             12.682                                                                             96250.6                                        4 hr., 120° C.                                                                1.6 9421.3                                                                             382.3                                                                              4954.6                                                                             12.131                                                                             96887.6                                        __________________________________________________________________________

Example 6

A test was performed on 10 pieces measuring 0.0185" ID×0.0235" OD tocheck for shrinkage. The pieces were made of Hytrel® 7246 as the outsidelayer, Plexar® 209 as the middle layer, and HDPE 6007 as the insidelayer. Parts were measured for i.d. with a mandrel, o.d. in two markedplaces, and length. They were annealed for 4 hours at 120° C. and foundto have no significant shrinkage in any parameter measured.

In sum, it has been found that medical tubing made according to thepresent invention allowed for good guidewire movement (with or withoutblood in lumen), traceability, ability to bend, crush resistance, kinkresistance, low profile, good tensile strength, coatability, costeffectiveness, gamma stability, and biocompatability.

Other embodiments of this invention will be apparent to those skilled inthe art upon consideration of this specification or from practices ofthe invention disclosed herein. Various omissions, modifications, andchanges to the principles and embodiments described herein may be madeby one skilled in the art without departing from the true scope andspirit of the invention which is indicated by the following claims. Forinstance, additional layers (e.g., a fourth layer) can be extrudedinside of the inner layer or outside of the outer layer. All documentscited herein are incorporated by reference in their entireties for allpurposes.

What is claimed is:
 1. A length of coextruded, flexible tubing suitablefor use in a medical device comprising:an outer layer comprising adirectly bondable polymer having a first glass transition temperature; acore layer defining a lumen extending through the length of tubing, saidcore layer comprising a lubricious polymer, said core layer having athird glass transition temperature; and an intermediate tie layercomprising a functionalized polymer having a second glass transitiontemperature; wherein the first, second and third glass transitiontemperatures are within 85% to 115% of the glass transition of the layeror layers adjacent thereto.
 2. The tubing of claim 1, wherein thepolymer of the outer layer is selected from a polyester, a polyamide, orcombinations thereof.
 3. The tubing of claim 2, wherein the polymer ofthe outer layer is a polyester.
 4. The tubing of claim 3, wherein thepolyester comprises at least one polyether segment and at least onepolyester segment.
 5. The tubing of claim 2, wherein the polymer of theouter layer is a polyamide.
 6. The tubing of claim 1, wherein thelubricious polymer of the core layer is selected from an olefinicpolymer, a fluorinated polymer or combinations thereof.
 7. The tubing ofclaim 6, wherein the lubricious polymer of the core layer is an olefinicpolymer.
 8. The tubing of claim 7, wherein the olefinic polymer isselected from high density polyethylene, ultra high densitypolyethylene, low density polyethylene, linear low density polyethylene,or combinations thereof.
 9. The tubing of claim 6, wherein thelubricious polymer of the core layer is a fluorinated polymer.
 10. Thetubing of claim 9, wherein the fluorinated polymer is polyvinylidenefluoride.
 11. The tubing of claim 1, wherein the intermediate tie layercomprises a polymer selected from an anhydride modified olefinicpolymer, an acrylate modified olefinic polymer or combinations thereof.12. The tubing of claim 11, wherein the polymer of the intermediate tielayer is selected from a functionalized polyethylene, a functionalizedvinylic polymer, a ethylene-methyl acrylate copolymer, an acid modifiedethyl vinyl acetate polymer, an acid modified ethylene acrylatecopolymer, an anhydride modified ethylene acrylate copolymer, ananhydride modified ethyl vinyl acetate copolymer, an acid modified ethylvinyl acetate polymer, an acrylate modified ethyl vinyl acetate polymer,an anhydride modified ethyl vinyl acetate copolymer, an anhydridemodified ethyl vinyl acetate polymer, or combinations thereof.
 13. Thetubing of claim 12, wherein the polymer of the intermediate tie layer isselected from a functionalized polyethylene, a functionalized copolymerobtained from monomers comprising ethylene and alleyl (meth)acrylate, ananhydride modified ethyl vinyl acetate polymer, or combinations thereof.14. A length of coextruded, flexible tubing suitable for use in amedical device comprising:an outer layer comprising a directly bondablepolymer selected from the group consisting of polyesters, polyamides, orcombinations thereof; a core layer defining a lumen extending throughthe length of tubing, said core layer comprising a lubricious polymer;and an intermediate tie layer comprising a functionalized polymer. acore layer defining a lumen extending through the length of tubing, saidcore layer comprising a lubricious polymer, said core layer having athird glass transition temperature; and an intermediate tie layercomprising a functionalized polymer.
 15. The tubing of claim 14, whereinthe third glass transition temperature is greater than the second glasstransition temperature and the second glass transition temperature isgreater than the first glass transition temperature.
 16. A medicaldevice adapted for percutaneous transluminal use comprising:a length ofcoextruded, tubing comprising:an outer layer comprising a directlybondable polymer having a first glass transition temperature; a corelayer defining a lumen extending through the length of tubing, said corelayer comprising a lubricious polymer, said core layer having a thirdtransition temperature, and an intermediate tie layer comprising afunctionalized polymer having a second glass transition temperature,wherein the first, second and third glass transition temperatures arewithin 85% to 115% of the glass transition of the layer or layersadjacent thereto; and a radially expansive component coupled to thelength of tubing.
 17. The medical device of claim 16, wherein theradially expansive component is a balloon.
 18. The medical device ofclaim 17, wherein the balloon is directly bonded to the outer layer ofthe tubing at the distal end of the balloon.
 19. The medical device ofclaim 18, wherein the balloon is thermally bonded to the outer layer ofthe tubing at its the distal end of the balloon.
 20. The medical deviceof claim 18, wherein the balloon is fusion bonded to the outer layer ofthe tubing at its the distal end of the balloon.
 21. The medical deviceof claim 17, wherein the tubing defines a guidewire lumen.
 22. Themedical device of claim 21, wherein the guidewire lumen extends throughthe entire length of the medical device.
 23. The medical device of claim22, wherein the medical device is an over-the-wire catheter.
 24. Themedical device of claim 21, wherein the distal end of the guidewirelumen exits through the distal end of the medical device and theproximal end of the guidewire lumen exits through a side wall of themedical device.
 25. The medical device of claim 24, wherein the medicaldevice is a rapid exchange catheter.
 26. The medical device of claim 16,wherein the polymer of the outer layer is selected from a polyester, apolyamide, or combinations thereof.
 27. The medical device of claim 26,wherein the polymer of the outer layer is a polyester.
 28. The medicaldevice of claim 27, wherein the polyester comprises at least onepolyether segment and at least one polyester segment.
 29. The medicaldevice of claim 26, wherein the polymer of the outer layer is apolyamide.
 30. The medical device of claim 16, wherein the lubriciouspolymer of the core layer is selected from an olefinic polymer, afluorinated polymer or combinations thereof.
 31. The medical device ofclaim 30, wherein the lubricious polymer of the core layer is anolefinic polymer.
 32. The medical device of claim 31, wherein theolefinic polymer is selected from high density polyethylene, ultra highdensity polyethylene, low density polyethylene, linear low densitypolyethylene, or combinations thereof.
 33. The medical device of claim30, wherein the lubricious polymer of the core layer is a fluorinatedpolymer.
 34. The medical device of claim 33, wherein the fluorinatedpolymer is polyvinylidene fluoride.
 35. The medical device of claim 16,wherein the intermediate tie layer comprises a polymer selected from ananhydride modified olefinic polymer, an acrylate modified olefinicpolymer, or combinations thereof.
 36. The medical device of claim 35,wherein the polymer of the intermediate tie layer is selected from afunctionalized polyethylene, a functionalized vinylic polymer, aethylene-methyl acrylate copolymer, an acid modified ethyl vinyl acetatepolymer, an acid modified ethylene acrylate copolymer, an anhydridemodified ethylene acrylate copolymer, an anhydride modified ethyl vinylacetate copolymer, an acid modified ethyl vinyl acetate polymer, anacrylate modified ethyl vinyl acetate polymer, an anhydride modifiedethyl vinyl acetate copolymer, an anhydride modified ethyl vinyl acetatepolymer, or combinations thereof.
 37. The medical device of claim 36,wherein the polymer of the intermediate tie layer is selected from afunctionalized polyethylene, an ethylene-methyl acrylate copolymer, ananhydride modified ethyl vinyl acetate polymer, or combinations thereof.38. The medical device of claim 17, wherein the tubing has an outsidediameter of from about 0.5 millimeters to about 0.7 millimeters.
 39. Themedical device of claim 38, wherein the tubing has an outside diameterof from about 0.55 millimeters to about 0.63 millimeters.
 40. Themedical device of claim 39, wherein the tubing has an outside diameterof from about 0.4 millimeters to about 0.6 millimeters.
 41. The medicaldevice of claim 40, wherein the tubing has an inside diameter of fromabout 0.43 millimeters to about 0.51 millimeters.
 42. The medical deviceof claim 16, wherein the third glass transition temperature is greaterthan the second glass transition temperature and the second glasstransition temperature is greater than the first glass transitiontemperature.